Neutrophil-Extracellular Traps, Cell-Free DNA, and Immunothrombosis in Companion Animals: A Review.
Authors: Goggs Robert, Jeffery Unity, LeVine Dana N, Li Ronald H L
Journal: Veterinary pathology
Summary
# Editorial Summary Neutrophil extracellular traps (NETs)—web-like structures of DNA studded with antimicrobial proteins—represent a third defensive mechanism alongside degranulation and phagocytosis, enabling neutrophils to neutralise pathogens even after cell death through a process called NETosis. This review synthesises evidence that NETosis occurs across companion animal species (dogs, horses, and cats) and examines the dual nature of this response: whilst immunothrombosis provides genuine protective benefits during infection and innate immune activation, excessive or poorly-localised NET formation contributes actively to pathogenesis and tissue damage, particularly when traps occlude critical blood vessels. The authors detail established detection methods—including measurement of cell-free DNA, histones, high-mobility group box-1, microscopy, and flow cytometry—and critically appraise their reliability and application in veterinary medicine. Understanding the mechanisms driving NETosis in equine and companion animal patients opens therapeutic avenues beyond current anti-inflammatory approaches, potentially allowing clinicians to modulate rather than simply suppress these responses in conditions ranging from sepsis to thrombotic complications. For practitioners managing conditions with suspected immune or thrombotic components, this framework suggests that NET formation may be a measurable and therapeutically targetable process, though further species-specific research is needed to translate these insights into clinical protocols.
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Practical Takeaways
- •Understanding NETosis mechanisms may reveal new therapeutic targets to modulate excessive immunothrombosis in critical conditions affecting companion animals.
- •Measuring cell-free DNA and extracellular trap markers could become clinically useful diagnostic tools for assessing systemic inflammation severity in horses, dogs, and cats.
- •Clinicians should recognize that while NETosis aids innate immunity, excessive trap formation in damaged blood vessels can be harmful and may warrant anti-inflammatory or NET-inhibiting interventions.
Key Findings
- •Neutrophil extracellular traps (NETs) represent a third mechanism of pathogen combatting alongside degranulation and phagocytosis, consisting of extracellular DNA decorated with bactericidal proteins including elastase, myeloperoxidase, and cathepsins.
- •NETosis occurs in companion animals (dogs, horses, and cats) and actively contributes to pathogenesis when occurring to excess or in critical blood vessels.
- •Neutrophils can release extracellular traps through controlled cell death or vital NETosis, which allows DNA extrusion while maintaining cell viability.
- •Multiple measurement methods exist for identifying NETosis including cell-free DNA quantification, histone measurements, high-mobility group box-1 assessment, microscopy, and flow cytometry techniques.